The Laboratory of Immunodiagnosis of the Sloan-Kettering Institute has an established interest in the detection and characterization of human sarcoma-associated antigens. Extensive studies have been completed using allogeneic and syngeneic sera as sources of antibody. These studies have resulted in the discovery of 3 sarcoma-related antigens, S1, S2, and S3. Of these, 2, S1 and S3, are newly identified heterophile substances to which patients with sarcoma have an increased prevalence of antibody. Changes in S3 antibody titers have been related to tumor mass. Ongoing work suggests that S3 may be a genetic marker of susceptibilityu to sarcomas. Unfortunately the antigens identified to date are not sufficiently tumor-specific to be of diagnostic value. The recent development of hybridoma techniques and more quantitative immunologic assays has prompted us to turn to this new technology in an effort to extend our knowledge of internal and surface antigens of the human sarcoma cell. The study design considers progress made in the last few years in the classification of lymphoid cell tumors using monoclonal antibocy methods. Many of the antigens distinguishing lymphoid cells are differentiation markers. It is intended, therefore, to conduct a broad-screen for sarcoma-related monoclonal antibodies and then determine their relationship to mesenchymal differentiation antigens. An important early application of new information regarding mesenchymal cell subtypes would be to permit human sarcomas to be classified by immunologic markers in addition to the morphologic criteria which are now used and often given ambiguous results. Preliminary studies indicate that a byproduct of this effort will be the generation of monoclonal antibodies to heterophile determinants. Such monoclonal antibodies will be screened for their reactivity with sarcoma-associated heterophile antigens and may be of help in distinguishing those members of this antigen group whose expression is most strngly tumor-related.